Clements Abigail, Gaboriaud Fabien, Duval Jérôme F L, Farn Jacinta L, Jenney Adam W, Lithgow Trevor, Wijburg Odilia L C, Hartland Elizabeth L, Strugnell Richard A
Australian Bacterial Pathogenesis Program, The University of Melbourne, Parkville, Victoria, Australia.
PLoS One. 2008;3(11):e3817. doi: 10.1371/journal.pone.0003817. Epub 2008 Nov 26.
Analysing the pathogenic mechanisms of a bacterium requires an understanding of the composition of the bacterial cell surface. The bacterial surface provides the first barrier against innate immune mechanisms as well as mediating attachment to cells/surfaces to resist clearance. We utilised a series of Klebsiella pneumoniae mutants in which the two major polysaccharide layers, capsule and lipopolysaccharide (LPS), were absent or truncated, to investigate the ability of these layers to protect against innate immune mechanisms and to associate with eukaryotic cells. The capsule alone was found to be essential for resistance to complement mediated killing while both capsule and LPS were involved in cell-association, albeit through different mechanisms. The capsule impeded cell-association while the LPS saccharides increased cell-association in a non-specific manner. The electrohydrodynamic characteristics of the strains suggested the differing interaction of each bacterial strain with eukaryotic cells could be partly explained by the charge density displayed by the outermost polysaccharide layer. This highlights the importance of considering not only specific adhesin:ligand interactions commonly studied in adherence assays but also the initial non-specific interactions governed largely by the electrostatic interaction forces.
分析一种细菌的致病机制需要了解细菌细胞表面的组成。细菌表面是抵御先天性免疫机制的第一道屏障,同时介导与细胞/表面的附着以抵抗清除。我们利用了一系列肺炎克雷伯菌突变体,其中两种主要的多糖层,即荚膜和脂多糖(LPS)缺失或被截断,以研究这些层抵御先天性免疫机制以及与真核细胞结合的能力。发现单独的荚膜对于抵抗补体介导的杀伤至关重要,而荚膜和LPS都参与细胞结合,尽管通过不同机制。荚膜阻碍细胞结合,而LPS糖类以非特异性方式增加细胞结合。这些菌株的电流体动力学特征表明,每种细菌菌株与真核细胞的不同相互作用部分可以通过最外层多糖层显示的电荷密度来解释。这突出了不仅要考虑在黏附试验中通常研究的特定黏附素:配体相互作用,还要考虑主要由静电相互作用力控制的初始非特异性相互作用的重要性。